Category Archives: Chronic pain

07Apr/12

Tackling chronic pain – it’s like learning a new language..and unlearning an old

Tackling chronic pain is a challenge. Undoubtedly our understanding of pain, the role of the nervous system and other body systems, has advanced to permit a reconceptualisation of the experience and how we can approach it. The knowledge that there is a form of conditioning and learning that goes on, means that we can switch our thinking to address these mechanisms. Clearly a change in reasoning was and continues to be required to be more effective in dealing with persisting pain.

I often use the analogy of learning a language with patients. Most people at some stage have had to go through this process, with some more natural than others at developing the skill. Equally, the thought of learning a musical instrument provokes a similar comparison. What is needed? Understanding, time, motivation and practice are certainly necessary ingredients. We also require adequate rest and sleep to cement the changes in brain function that occurs as a result of its plasticity.

So what has been learned in chronic pain?

We can divide this into biological responses and behaviours that we purposely adopt. The brain learns to produce pain and becomes very good in some cases, creating the experience even when it is not required–recalling that pain is an output from the brain in response to a perceived threat based upon the danger (nociceptive) signals received from the body via the spinal cord; the caveat being that nociceptive signals and the act of nociception is neither needed nor necessary for the brain to create pain. Equally, nociception can be ticking on but without the brain producing the conscious experience of pain. This means that as soon as the brain is sure we are under threat, it will protect us with pain and concurrent responses. These include changes in movement, activity in the endocrine system (hormones) and the immune system that pervades our body as a second nervous system.

‘..pain cannot exist out of consciousness. In contrast, but often erroneously considered analogous, nociception can exist outside of consciousness. In fact, nociception can occur without the brain–high-threshold peripheral afferents and their spinal projections can be activated in the absence of brain activity. Indeed, tactile perception, pain and other bodily feelings can be thought of as outputs of the brain that are based on an informed interpretation of the information coming from one’s body.’ Taken from Moseley & Flor (2012)

The way we respond to pain is individual and learned from previous experiences. Clearly it is both useful and vital to learn that an oven is hot and a pin is sharp. Acute pain is an incredible device and one of the body’s responses to perceived danger. In persisting pain states, arguably the pain is not useful or promoting adaptive behaviours. Although, when the tissues are not as healthy as they may be, the peripheral nervous system is sensitive and movement is not normal, perhaps some level of pain is useful as a motivator to develop healthier tissues. Undoubtedly though, in many cases of chronic pain, the intensity and impact far outweighs any benefit. The incredible sensitivity, robust and lengthy responses to normal activities cause utter havoc and enormous distress such as in the case of complex regional pain syndrome.

Approaching the problem of chronic pain requires a 360 view on the individual. Understanding pain mechanisms, limitations, social impact and influential factors are all important in the planning of a treatment programme. In addition, as argued here, considering chronic pain as a learned response on different levels is a useful way of conceptualising the problem in terms of understanding how the situation has evolved and how it must be tackled.

RS

04Apr/12

Reconceptualising pain for better treatment – a revolution? A revelation?

Traditionally pain is understood to be an unpleasant experience in the body where a problem exists, and is something to be got rid of as quickly as possible. The so-called ‘biomedical model’ considers which structures require treatment or surgery, stopping at the tissues as the cause of pain. This paradigm has been challenged over the years and rightly so in the light of recent research. Many studies have revealed the underlying physiology within the nervous system, and in particular the brain, and the role of other body systems such as the immune system and endocrine system (hormones) in pain. Understanding that pain is a normal response to a perceived threat has helped mould new treatments and ways of dealing with pain.

The most pertinent discovery and emergent shift in thinking came when it was realised that pain is a brain experience. This came via studies of the brain but also by looking at why phantom limb pain exists and how people present with a range of injuries and such varied levels of reported pain. There are many stories of people suffering severe physical injury yet experience little or no pain at the time.

The fact that we know pain is a brain experience has helped us to understand the many influences upon the pain, especially one’s emotional state. For instance, we know that the danger signals that are sent by the body to the brain via the spinal cord, travel to the emotional centres of the brain to try and give some meaning to the pain. These signals reach the brain and receive scrutiny to work out the level of threat, and this can vary enormously depending upon a range of factors. On activating a widespread group of neurons termed the ’pain matrix’, the output from the brain, a response, can be the pain experience. Knowing that there are many parts of the brain involved has meant that there are now a range of approaches that can tackle the problem of pain.

We are now far more optimistic about treating pain. This is not just with medication, which does have a role when used wisely, but with a range of contemporary treatments, strategies and techniques that address the underpinning mechanisms at a tissue level, spinal cord level and a brain level alongside beliefs, attitudes and behaviours that can be moulded to change the pain. The term used to describe the contemporary approach to pain is ’biopsychosocial’, implying a role for the overlapping biological, psychological and social factors that must be addressed.

29Mar/12

It’s tight…it’s being protected

Tightness in the muscle is a common complaint. Often part of a profile of symptoms following an injury and frequently a stand alone sense that persists, tightness and stiffness need addressing to normalise movement and control of movement. Normalising movement is a key part of desensitisation in that it is one less reason for the body to protect itself.

Tightness can be an expression of protection – what is being protected and why?

To address persisting tightness we must determine why and what is being protected. There could healing tissue, a pocket of inflammation or sensitivity to movement within the nervous system (mechanosensitivity). A detailed assessment of the problem, the preceding history and prior events reveal the nature and underpinning source(s), i.e. biological mechanisms. These mechanisms are then targeted with appropriate treatment and strategies.

A common treatment method that we use is called neurodynamics. This is a range of hands-on techniques and movement-based exercises that nourish and mobilise the nervous system. Bearing in mind that our tissues will only be as healthy as the nerves that supply them (a general rule of thumb, but other factors are important including the immune system and endocrine system), it is very important that the nervous system be moving and its blood supply patent.

Tightness can be a sign of guarding. Guarding is protection orchestrated by the brain and can occur at a motor planning level. This means that before moving, the brain increases the activity of certain muscles as a way of protecting a body region for when movement actually occurs. A common example of guarding is in the case of back pain when the muscles remain ‘on’ as the spine is flexed forwards. These muscles should switch off and relax, however the fact that they remain active means that the movement is not normal. Addressing this is important for re-establishing motor control.

Local treatments are often used and can help in the short-term. However, these should be used as part of a rounded programme addressing the pain, symptoms, impact, limitations and other dimensions of the problem. Delving into the details and observing the sometimes subtle changes in movement and control of movement allows us to elucidate the reason(s) for protection and deal with persisting tightness.

12Feb/12

Pain Mechanisms – what underpins our pain?

Understanding pain mechanisms is the key to effective treatment. The mechanisms that have been studied, written about in science journals and discussed with patients include nociceptive pain, inflammatory pain, neuropathic pain and central sensitisation. Elucidating which are playing a role in the patient’s experience allows the doctor to prescribe the right medication and the modern physical therapist to address the issues of pain in a biopsychosocial manner. I will now clarify the latter point.

In taking a detailed history, observing patterns of movement and protection, assessing the state of the nervous system and health of the body systems, understanding behaviours and the beliefs behind them and learning of the influences upon the individual’s pain experience, one can know about the likely pain mechanisms underpinning the experience. From here the treatment strategies can be chosen to target these mechanisms. For example, top-down approaches for central sensitisation focus on the change in the properties of the central nervous system. The interventions themselves are observant of the amplification that occurs in the spinal cord and higher centres and would seek to dampen the responses with input to the brain that is perceived as normal or non-threatening. This could include sensory stimulation or movements outside of the receptive field, education to reduce fear of movement or imagery to name but a few. Inflammatory pain can also be treated with a top-down approach but local tissue based strategies would also be used. Just to note that the separation of the ‘top end’ (brain and spinal cord) from ‘bottom end’ (tissues) is really a false dichotomy as all conscious experiences are from the brain including what we see and what we feel.

Stephen McMahon and David Bennett, both experts in the field of pain science from King’s College London, produced a poster that describes these mechanisms – click here to visit the page in Nature Reviews Neuroscience. This is what they say about it:

Pain is an unpleasant sensation resulting from the intricate interplay between sensory and cognitive mechanisms. Chronic pain, resulting from disease or injury, affects nearly every fifth person in the Western world, constituting an enormous burden for the individual and society. Sensitization of pain signalling systems is a key feature of chronic pain and results in normally non-painful stimuli eliciting pain. Such sensory changes can occur not just at the sites of injury, but in surrounding normal tissues. This and other observations suggest that sensitization occurs within the CNS as well as within nociceptor terminals. Here we consider the consequences of noxious stimulus applied to our unfortunate builder’s hand, from sensory transduction to pain perception. We describe the structural and functional elements present at different levels of the nociceptive system, as well as some of the changes occurring in chronic pain states. Although our poster highlights a flow of information from the periphery to the CNS, it should be noted that higher brain centres exert both inhibitory and facilitatory controls on lower ones. The challenge for the next decade will be to effectively translate this knowledge into the development of novel analgesic agents for better pain relief.

11Feb/12

Manual therapy, pain and the immune system

As a physiotherapist I frequently use my hands to treat the joints and tissues. It comes with the territory, everyone expects hands-on therapy and it does helps to reduce tension and pain. Most likely, the pain relief from joint mobilisation is due to descending mechanisms that include those that are powered by serotonin and noradrenaline (see here). This is very useful to know as it tells us about the effects of passively moving joints and importantly permits wise selection of techniques to target the pain mechanisms. Building on the knowledge base, two very recent studies have identified some extremely interesting results.

Firstly, Martins et al. (2011) found that ankle joint mobilisation reduced pain in a neuropathic pain model in rats along with seeing the regeneration of nerve tissue and inhibition of glial cell activation (a blog will be coming soon that discusses the immune system in pain states) in the dorsal horn of the spinal cord. Secondly, Crane et al. (2012) looked at how massage helps reduce the pain of exercise-induced muscle damage in young males. Taking muscle biopsies they found that massaged subjects demonstrated attenuation of proinflammatory cytokines, key players in sensitisation. It was also noted that massage had no effect upon metabolites such as lactate – see below.

More research into the mechanisms that underpin the effects of hands-on therapy is needed despite the advancements in our understanding. The ability to focus treatment upon this understanding can only develop our effectiveness in treating pain. I am very optimistic about the movement forwards in pain and basic science, and how this can be applied  in our thinking with individual patients. The language is changing with the words ‘treatment’ being used rather than ‘management’, the latter of which can imply that one has reached their limit of improvement. This is exciting and more importantly, realistic when one considers therapies such as the graded motor imagery. We do not have treatments that work for all pains but we do have brains and body systems that are flexible, dynamic and can change if given the opportunity, the right stimulation within the right context on the background of good understanding. It is our duty to keep this rolling onwards and thinking hard about how to best use the findings such as those highlighted in this blog.

Pain. 2011 Nov;152(11):2653-61. Epub 2011 Sep 8.

Ankle joint mobilization reduces axonotmesis-induced neuropathic pain and glial activation in the spinal cord and enhances nerve regeneration in rats.

Martins DF, Mazzardo-Martins L, Gadotti VM, Nascimento FP, Lima DA, Speckhann B, Favretto GA, Bobinski F, Cargnin-Ferreira E, Bressan E, Dutra RC, Calixto JB, Santos AR.

Source

Laboratório de Neurobiologia da Dor e Inflamação, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.

Abstract

An important issue in physical rehabilitation is how to protect from or to reduce the effects of peripheral nerve injury. In the present study, we examined whether ankle joint mobilization (AJM) would reduce neuropathic pain and enhance motor functional recovery after nerve injury. In the axonotmesis model, AJM during 15 sessions every other day was conducted in rats. Mechanical and thermal hyperalgesia and motor performance deficit were measured for 5 weeks. After 5 weeks, we performed morphological analysis and quantified the immunoreactivity for CD11b/c and glial fibrillary acidic protein (GFAP), markers of glial activation, in the lumbar spinal cord. Mechanical and thermal hyperalgesia and motor performance deficit were found in the Crush+Anesthesia (Anes) group (P<0.001), which was significantly decreased after AJM (P<0.001). In the morphological analysis, the Crush+Anes group presented reduced myelin sheath thickness (P<0.05), but the AJM group presented enhanced myelin sheath thickness (P<0.05). Peripheral nerve injury increased the immunoreactivity for CD11b/c and GFAP in the spinal cord (P<0.05), and AJM markedly reduced CD11b/c and GFAP immunoreactivity (P<0.01). These results show that AJM in rats produces an antihyperalgesic effect and peripheral nerve regeneration through the inhibition of glial activation in the dorsal horn of the spinal cord. These findings suggest new approaches for physical rehabilitation to protect from or reduce the effects of nerve injury.

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Sci Transl Med. 2012 Feb 1;4(119):119ra13.

Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage.

Crane JD, Ogborn DI, Cupido C, Melov S, Hubbard A, Bourgeois JM, Tarnopolsky MA.

Source

Department of Kinesiology, McMaster University, Hamilton, Ontario L8S 4L8, Canada.

Abstract

Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)], and mitigated the rise in nuclear factor κB (NFκB) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis.

03Feb/12

Chronic pain in sport – Specialist Clinic in London

Chronic pain is a real problem in the sporting world. The effects of not being able to participate are far reaching, especially when sport is your profession. There are a huge numbers of clinics offering treatments to deal with pain and injury and in many cases the problem improves. However, there are those who do not progress successfully, resulting in on-going pain, failed attempts to return to playing and varied responses to tissue-based treatment (manual therapy, injections, surgery etc). Understanding more about pain and how your body (brain) continues to protect itself is a really useful start point in moving forwards if you have become stuck. We know that gaining knowledge about the problem can actually improve a clinical test and the pain threshold.

When we injure ourselves playing sport the healing process begins immediately. Chemicals released by the tissues and the immune system are active locally, sealing off the area, dealing with the damaged tissue and setting the stage for rebuilding and repair. The pain asscociated with this phase is expected, normal and unpleasant. It is the unpleasantness that drives you to behave in a protective manner, for example limp, seek advice and treatment. Again, that is normal. Sometimes we can injure ourselves and not know that we have damaged the tissues. There are many stories of this happening when survival or something else is more important. This is because pain is a brain (not mind or ‘in the head’) experience 100% of the time. The brain perceives a threat and then protects the body. If no threat is perceived or it is more important to escape or finish the cup final, the brain is quite capable of releasing chemicals (perhaps 30 times more powerful than morphine) to provide natural pain relief. We know that pain is a brain experience because of phantom limb pain, a terrible situation when pain is felt in a limb that no longer exists. The reason is that we actually ‘feel’ or ‘sense’ our bodies via our virtual body that is mapped out in the brain. This has been mapped out by some clever scientists and in more recent years studies intensely using functional MRI scans of the brain.

Unfortunately, the brain can continue to protect the body with pain and altered movement beyond the time that is really useful. Changes in the properties of the neurons in the central nervous system (central sensitisation) mean that stimuli that are normally innocuous now trigger a painful response as can those outside of the affected area. One way to think about this functionality is that the gain or volume has been turned up, and we know that much of this amplification occurs in the spinal cord, involving both neurons and the immune system. Neurogenic inflammation can also be a feature, where the C-fibres release inflammatory chemicals into the tissues that they supply. On the basis that the brain is really interested in inflammation, even a small inflammatory response can evoke protective measures. Changes in the responsiveness of the ‘danger’ system as briefly described, underpin much of the persisting sensitivity. Altered perception is a further common description, either in the sense that the area is not controlled well or feels somewhat different – see here.

As the problem persists, so thinking and beliefs about the pain and injury can become increasingly negative. Unfortunately this can lead to behaviours that do not promote progression. Avoidance of activities, fear of movement, hypervigilance to signals from the body and catastrophising about the pain are all common features, all of which require addressing with both pain education and positive experiences to develop confidence and deeper understanding. An improvement in the pain level is a great way of starting this process, hence the importance of a tool box of therapies and strategies that target the pain mechanism(s) identified in the assessment.

Experience and plenty of scientific data describe the integration of body, brain and mind. This can no longer be ignored. It is fact. The contemporary biobehavioural approach to chronic and complex pain addresses the pain mechanisms, issues around the problem and the influencing factors in a biopsychosocial sense:

  • Biology: e.g./ physiology of pain, body systems involved in protection, tissue health
  • Psychology: e.g./ fears, anxiety, beliefs about the pain, thinking processes, outlook, coping, past experiences
  • Social: e.g./ work effects, effect upon the family, socialising, role of significant others (spouse, family), financial considerations

Specialist Clinic in London and Surrey for chronic pain and injury in sport – call 07518 445493

Chronic pain and injury requires an all-encompassing biobehavioural approach. Although the end aims can be different, the structure and themes within the treatment programme are similar to those that tackle any chronic pain issue. Bringing these principles into the sports arena, we can incorporate traditional models of care and advance beyond the tissue-based strategies to a way of working that addresses the source of the problem alongside the influencing factors that are slowing or even preventing recovery.

If you as a player are struggling to move forwards or have a player on your team who is not recovering or failing to respond as expected to treatment, we would be very pleased to help you. Call 07518 445 493 or email [email protected] for further infomartion about the clinics:

The Specialist Pain Physio Clinics work closely with the very best Consultants and can organise investigations such as MRI scans and x-rays with reports rapidly, an on-site at the New Malden Diagnostic Centre, 9 Harley Street and in Chelsea.

21Jan/12

Central sensitisation is more common than you may think

Clifford Woolf recently said this about central sensitisation:

Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

And Latremolier

Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury. The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification. Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity. Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations. PERSPECTIVE: In this article, we review the major triggers that initiate and maintain central sensitization in healthy individuals in response to nociceptor input and in patients with inflammatory and neuropathic pain, emphasizing the fundamental contribution and multiple mechanisms of synaptic plasticity caused by changes in the density, nature, and properties of ionotropic and metabotropic glutamate receptors.

In essence we are talking about changes within the central nervous system that underpin the widespread, unpredictable and varied nature of persisting pain.

When I am listening to a patient, observing their movements and performing a ‘multi-system’ examination, I am in part looking for the pain mechanisms at play, including central sensitisation. Several of my questions are: ‘what is going on here to create this experience for the person in front of me?’, ‘why are the nervous and other systems responding in such a way?’ and ‘what is influencing the behaviour of those systems?’. I really need to know what it is that is prolonging this protection and is it really worthwhile for the individual.

Suspecting that there is a component of central sensitisation at play in many cases of chronic pain that I see, it is pleasing to see a group looking at this closely and finding evidence to support this thinking:

J Bone Joint Surg Br. 2011 Apr;93(4):498-502.

Evidence that central sensitisation is present in patients with shoulder impingement syndrome and influences the outcome after surgery.

Gwilym SE, Oag HC, Tracey I, Carr AJ.

Source

Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK. [email protected]

Abstract

Impingement syndrome in the shoulder has generally been considered to be a clinical condition of mechanical origin. However, anomalies exist between the pathology in the subacromial space and the degree of pain experienced. These may be explained by variations in the processing of nociceptive inputs between different patients. We investigated the evidence for augmented pain transmission (central sensitisation) in patients with impingement, and the relationship between pre-operative central sensitisation and the outcomes following arthroscopic subacromial decompression. We recruited 17 patients with unilateral impingement of the shoulder and 17 age- and gender-matched controls, all of whom underwent quantitative sensory testing to detect thresholds for mechanical stimuli, distinctions between sharp and blunt punctate stimuli, and heat pain. Additionally Oxford shoulder scores to assess pain and function, and PainDETECT questionnaires to identify ‘neuropathic’ and referred symptoms were completed. Patients completed these questionnaires pre-operatively and three months post-operatively. A significant proportion of patients awaiting subacromial decompression had referred pain radiating down the arm and had significant hyperalgesia to punctate stimulus of the skin compared with controls (unpaired t-test, p < 0.0001). These are felt to represent peripheral manifestations of augmented central pain processing (central sensitisation). The presence of either hyperalgesia or referred pain pre-operatively resulted in a significantly worse outcome from decompression three months after surgery (unpaired t-test, p = 0.04 and p = 0.005, respectively). These observations confirm the presence of central sensitisation in a proportion of patients with shoulder pain associated with impingement. Also, if patients had relatively high levels of central sensitisation pre-operatively, as indicated by higher levels of punctate hyperalgesia and/or referred pain, the outcome three months after subacromial decompression was significantly worse.

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Arthritis Rheum. 2009 Sep 15;61(9):1226-34.

Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients.

Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, Chessell I, Tracey I.

Source

University of Oxford, Oxford, UK. [email protected]

Abstract

OBJECTIVE:

The groin pain experienced by patients with hip osteoarthritis (OA) is often accompanied by areas of referred pain and changes in skin sensitivity. We aimed to identify the supraspinal influences that underlie these clinical manifestations that we consider indicative of possible central sensitization.

METHODS:

Twenty patients with hip OA awaiting joint replacement and displaying signs of referred pain were recruited into the study, together with age-matched controls. All subjects completed pain psychology questionnaires and underwent quantitative sensory testing (QST) in their area of referred pain. Twelve of 20 patients and their age- and sex-matched controls underwent functional magnetic resonance imaging (MRI) while the areas of referred pain were stimulated using cold stimuli (12 degrees C) and punctate stimuli (256 mN). The remaining 8 of 20 patients underwent punctate stimulation only.

RESULTS:

Patients were found to have significantly lower threshold perception to punctate stimuli and were hyperalgesic to the noxious punctate stimulus in their areas of referred pain. Functional brain imaging illustrated significantly greater activation in the brainstem of OA patients in response to punctate stimulation of their referred pain areas compared with healthy controls, and the magnitude of this activation positively correlated with the extent of neuropathic-like elements to the patient’s pain, as indicated by the PainDETECT score.

DISCUSSION:

Using psychophysical (QST) and brain imaging methods (functional MRI), we have identified increased activity with the periaqueductal grey matter associated with stimulation of the skin in referred pain areas of patients with hip OA. This offers a central target for analgesia aimed at improving the treatment of this largely peripheral disease.

18Jan/12

Contemporary understanding of factors in joint pain

Recent research has identified biological reasons for joint pain in arthritis:

  • Interleukin-6, a pro-inflammatory cytokine released both locally at the joint and in the spinal cord, consequently plays a role in the widespread nature of the pain via its role in central sensitisation.
  • Sprouting of sensory and sympathetic fibres at the joint may well have a role in sensitisation
  • Angiogenesis, the growth of new blood vessels, at the joint, perhaps having a role in inflammation

Some of this may sound familiar. IL-6 is known to play a role in the spinal cord following nerve injury, sprouting of the sympathetic fibres at the DRG and in tendinopathy, and angiogenesis also seen in tendinopathy. All are clearly responses by the body and are involved in pain–remembering that pain is a brain experience 100% of the time of course.

Spinal interleukin-6 is an amplifier of arthritic pain (Vazquez et al. 2011)

Objective.

Significant joint pain is usually widespread beyond the afflicted joint which results from the sensitization of nociceptive neurons in the central nervous system (central sensitization). In the present study we explored (a) whether the proinflammatory cytokine interleukin-6 (IL-6) in the joint induces central sensitization, (b) whether joint inflammation causes IL-6 release in the spinal cord, and (c) whether spinal IL-6 contributes to central sensitization.

Methods.

In anesthetized rats electrophysiological recordings were made from spinal cord neurons with sensory input from the knee joint. Neuronal responses to mechanical stimulation of the knee and the leg were monitored. IL-6 and its soluble receptor sIL-6R were applied to the knee joint or the spinal cord. Spinal release of IL-6 was measured by ELISA. Sgp130 which neutralizes IL-6/sIL-6R was spinally applied during development of joint inflammation or during established inflammation.

Results.

A single injection of IL-6/sIL-6R into the knee joint as well as spinal application of IL-6/sIL-6R significantly increased the responses of spinal neurons to mechanical stimulation of the knee and ankle joint, i.e. induced central sensitization. Spinally applied sgp130 attenuated this IL-6 effect. Development of knee inflammation caused spinal release of IL-6. Spinal application of spg130 attenuated the development of inflammation-evoked central sensitization but did not reverse it.

Conclusions.

Not only IL-6 in the joint is involved in the generation of joint pain but also IL-6 which is released in the spinal cord. Spinal IL-6 contributes to central sensitization and thus promotes the widespread hyperalgesia in the course of joint disease.

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Neuroplasticity of sensory and sympathetic nerve fibers in the painful arthritic joint (Ghilardi et al. 2011)

Objective.

Many forms of arthritis are accompanied by significant chronic joint pain. Here we studied whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathological reorganization.

Methods.

A painful arthritic knee joint was produced by injection of complete Freund’s adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry using antibodies raised against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), growth associated protein-43 (GAP43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells) or CD68 (monocytes/macrophages).

Results.

In CFA-injected mice, but not vehicle-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, CGRP+, NF200+, GAP43+, and TH+ nerve fibers in the synovium as well as joint pain-related behaviors. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages.

Conclusions.

Ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain.

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Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis (Ashraf et al. 2011)

Objective

To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA).

Methods

OA was induced in male Lewis rats (n = 8 per group) by meniscal transection. Animals were orally dosed with dexamethasone (0.1 mg/kg/day), indomethacin (2 mg/kg/day), or the specific angiogenesis inhibitor PPI-2458 (5 mg/kg every other day). Controls consisted of naive and vehicle-treated rats. Synovial inflammation was measured as the macrophage fractional area (expressed as the percentage), thickness of the synovial lining, and joint swelling. Synovial angiogenesis was measured using the endothelial cell proliferation index and vascular density. Channels positive for vessels at the osteochondral junction were assessed (osteochondral angiogenesis). Medial tibial plateaus were assessed for chondropathy, osteophytosis, and channels crossing the osteochondral junction. Pain behavior was measured as weight-bearing asymmetry.

Results

Dexamethasone and indomethacin each reduced pain behavior, synovial inflammation, and synovial angiogenesis 35 days after meniscal transection. Dexamethasone reduced, but indomethacin had no significant effect on, the total joint damage score. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior.

Conclusion

Our findings indicate that synovial inflammation and joint damage are closely associated with pain behavior in the meniscal transection model of OA. Inhibition of angiogenesis may reduce pain behavior both by reducing synovitis and by preventing structural change. Targeting angiogenesis could therefore prove useful in reducing pain and structural damage in OA.

19Dec/11

Healthy tissues in 1-2-3

The simple fact is that our tissues need movement to be healthy. By tissues I am referring to muscles, tendons, ligaments, bones, fascia and skin. This does not need to be extreme movement but it must be regular and purposeful. Even without pathology, pain or an injury it is vital that the tissues are moved consistently throughout the day. It is likely that if you are recovering from a pain state, this movement will need to be ‘little and often’ to follow the principle of ‘motion is lotion’. I love this phrase. It was coined by the NOI Group guys and I use it frequently. At the moment I a considering some other phrases with similar meanings. If anyone has any suggestions please do comment below.

There are many types of movement from simple stretching to walking and more structured exercise such as yoga.  For convenience I talk to patients about the ‘themes’ of the treatment programme. In relation to movement there are three themes 1-2-3: specific exercises to re-train normal movement and control of movement, general exercise and the self-care strategies to be used throughout the day.

The specific exercises could include re-learning to walk normally, to re-establish normal control of the ankle or to concurrently develop confidence such as in bending forwards in cases of back pain. Normal control of movement is a fundamental part of recovery. When the information from the tissues to the brain is accurate, there is a clear view on what is happening, menaing that the next movement is efficient and so on.

General exercise is important for our health in body and mind. As well as reducing risk of a number of diseases, our brains benefit hugely from regular exercise. We release chemicals such as serotonin that make us feel good, endorphins that ease pain and BDNF that works like a miracle grow for brain cells. Gradually increasing exercise levels is a part of the treatment programme for all of these reasons.

Regularly punctuating static positions with movement nourishes the tissues and the brain’s representation of the body. The tissues will tighten and stiffen when they remain in one position for a long period of time, and more so when there is pathology or pain. Often there is already overactivity in the muscular system when we are in pain as part of the way the brain defends the body. This overactivity leads to muscle soreness that can be eased with consistent movement.

These three simple measure are behaviours. Behaviours are based on our belief system and therefore we need to understand why it is so important to move and re-establish normal control of movement as part of recovering from an injury or pain state. This includes tackling any issues around fear of movement and hypervigilance towards painful stimuli from the body. Our treatment programmes address these factors comprehensively, employing the biopsychosocial model of care and the latest neuroscience based knowledge of pain.

Email [email protected] for more information about our treatment programmes or to book an appointment.

21Oct/11

Using neuroscience to understand and treat pain

I love neuroscience. It makes my job much easier despite being a hugely complex subject. Neuroscience research has cast light over some of the vast workings of our brains and helped to explain how we experience ourselves and the richness of life. An enormous topic, in this blog I am briefly going to outline the way in which I use contemporary neuroscience to understand pain and how we can use this knowledge to treat pain more effectively. This is not about the management of pain, it is the treatment of pain. Management of pain is old news.

Understanding pain is the first step towards changing the painful experience. Knowing how the brain and nervous system operate allows us to create therapies that target the biological mechanisms that underpin pain. Appreciation of the plastic ability of the nervous system from top to bottom–brain to periphery–provides us with the opportunity to ‘re-wire’, and therefore to alter the function of the system and make things feel better. Knowing the role of the other body systems when the brain is defending us, is equally important. The synergy of inputs from the immune system, endocrine system and autonomic nervous system provides the brain with infomration about our internal physiology that it must scrutinse and act upon in the most appropriate way. We call this action the brain’s ‘output’ which is the responses that it co-ordinates to promote health and survival.

Excellent data from contemporary research tells us that understanding pain increases the pain threshold (harder to trigger pain), reduces anxiety in relation to pain and enhances our ability to cope and deal with the pain. We know that movement can also improve after an education session. This is because the perceived threat is reduced by learning and understanding what is going on inside, and knowing what can be done. The vast majority of patients who come to the clinic do not know why their pain has persisted, what pain really is, how it is influenced and what they can do about it themselves. For me this is the start point. Explaining the neuroscience of pain. Facts that we know people can absorb, understand and apply to themselves in such a way that the brain changes and provides a different experience.

It is the brain that gives us our experience of ourselves and the world around us. This includes the sensory and emotional experience of pain. The brain receives information from the body via the peripheral nervous system that suggests there is a threat to the tissues (input). In response, the brain must decide whether this threat is genuine based upon what is happening at the time, the emotional state, past experience, the belief system, gender, genetics, health status, culture and other factors. In the case that the brain perceives a threat, the output will be pain. The Mature Organism Model developed by Louis Gifford describes this beautifully (see below).

Pain is a motivator. It grabs our attention in the area of the body that the brain feels is threatened based upon the danger signals it is receiving from the tissues via the spinal cord. The brain actually ascribes the location of the pain via the map of the body that exist in the sensory cortex. On feeling the pain, we take action. This is the reason for pain. It motivates us to move, seek help or rest. Pain is an incredible device that we have for survival and learning, necessary to navigate life and completely normal. The brain constructs the pain experience and associated symptoms in such a way that we have to take note and do something about it immediately.